Cancer cells may regulate host immune system to evade from immune surveillance. Several approaches had been developed to reactivate the immune system in tumor microenvironment and restore T cell ability to eradicate cancer cells. One of these approaches is immune-checkpoint targeting based on blocking the receptors that normally inhibit the immune response, such as Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) and Programmed death 1 (PD1). Ipilimumab, an antagonistic antibody (mAb) against CTLA-4, was approved for the treatment of advanced melanoma in 2011 by FDA. Recently, inhibitory antibody against PD-1 was proved in clinical trial to be effectively in treatment of melanoma and non-small-cell lung cancer (NSCLC).
PD-1 is named for its highly express on dying cells and involve in the process of program cell death. PD-1 is a type I transmembrane protein containing extracellular domain belongs to immunoglobulin superfamily and intracellular domain containing an immunoreceptor tyrosine-based inhibitory motif (ITIM). Similar to CTLA-4 receptor, PD-1 is also a powerful inhibitory receptor that inhibits T cell activation. However the signaling pathway analysis reveals that PD-1 and CTLA-4 inhibit T cell activation by distinct mechanism and dual treatment of CTLA-4 and PD-1 antagonistic antibody can induce a synergistic effect. Moreover, compare to CTLA-4 that only express on T cell, PD-1 majorly express on activated T cell, B cell and macrophage. The boarder distribution of PD-1 receptor suggests it might be involved in more widely role in immune regulation. All these finding indicated that molecules which capable to block PD-1 pathway might hold a great potential in anticancer immunotherapy.
Aptamers are short DNA or RNA molecules that are capable of forming secondary structure or even complex three-dimensional structures. Aptamer technology has progressed tremendously since its discovery in the early 1990s. Aptamers have several advantages that make it suitable for therapeutic application, including lower molecular weight that allows it easier to penetrate through tissue than antibody, low cost in chemical synthesis, established modification methods and high stability. It is therefore of great interest to develop suitable aptamers having high affinity to a target protein.